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J. Cell Biol.,
Volume 143, Number 7, December 28, 1998 1899-1918
Laboratory of Cell Biology, Section on Molecular Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of
Health, Bethesda, Maryland 20892
Unlike wild-type mouse melanocytes, where
melanosomes are concentrated in dendrites and dendritic tips, melanosomes in dilute (myosin Va
) melanocytes are concentrated in the cell center. Here we
sought to define the role that myosin Va plays in melanosome transport and distribution. Actin filaments
that comprise a cortical shell running the length of the
dendrite were found to exhibit a random orientation,
suggesting that myosin Va could drive the outward spreading of melanosomes by catalyzing random walks.
In contrast to this mechanism, time lapse video microscopy revealed that melanosomes undergo rapid (~1.5
µm/s) microtubule-dependent movements to the periphery and back again. This bidirectional traffic occurs
in both wild-type and dilute melanocytes, but it is more
obvious in dilute melanocytes because the only melanosomes in their periphery are those undergoing this
movement. While providing an efficient means to transport melanosomes to the periphery, this component does not by itself result in their net accumulation there.
These observations, together with previous studies
showing extensive colocalization of myosin Va and
melanosomes in the actin-rich periphery, suggest a
mechanism in which a myosin Va-dependent interaction of melanosomes with F-actin in the periphery prevents these organelles from returning on microtubules
to the cell center, causing their distal accumulation.
This "capture" model is supported by the demonstration that (a) expression of the myosin Va tail domain
within wild-type cells creates a dilute-like phenotype via a process involving initial colocalization of tail domains with melanosomes in the periphery, followed by
an ~120-min, microtubule-based redistribution of melanosomes to the cell center; (b) microtubule-dependent melanosome movement appears to be damped by
myosin Va; (c) intermittent, microtubule-independent,
~0.14 µm/s melanosome movements are seen only in
wild-type melanocytes; and (d) these movements do
not drive obvious spreading of melanosomes over 90 min. We conclude that long-range, bidirectional, microtubule-dependent melanosome movements, coupled
with actomyosin Va-dependent capture of melanosomes in the periphery, is the predominant mechanism
responsible for the centrifugal transport and peripheral
accumulation of melanosomes in mouse melanocytes.
This mechanism represents an alternative to straightforward transport models when interpreting other myosin V mutant phenotypes.
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